Assessment of Dehydration in Children with Diarrhea in Resource-Limited Settings

资源有限环境下腹泻儿童脱水的评估

• 批准号: 9281928
• 负责人: Adam Carl Levine
• 金额: $ 13.41万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9281928
• 关键词: Adverse event; Affect; Area; Bangladesh; Body Weight Changes; California; Caring; Cessation of life; Child; Childhood; Clinical; Clinical Trials Design; Clinics and Hospitals; Cost Effectiveness Analysis; Country; Data; Dehydration; Developing Countries; Development; Diagnosis; Diagnostics Research; Diarrhea; Disease; Disease Outbreaks; Effectiveness; Ethics; Foundations; Functional disorder; Funding; Gold; Grant; Guidelines; Health; Healthcare; IV Fluid; Income; Inferior vena cava structure; International; Intervention; K-Series Research Career Programs; Knowledge; Lead; Length of Stay; Liquid substance; Malnutrition; Master of Public Health; Measures; Medicine; Mentored Research Scientist Development Award; Mentorship; Methods; Morbidity - disease rate; Nurses; Oral; Outcome; Pattern; Physicians; Physiological; Population; Prospective Studies; Public Health; Public Health Schools; Randomized Controlled Trials; Reading; Receiver Operating Characteristics; Refugee Camp; Regression Analysis; Rehydration Solutions; Rehydrations; Research; Resources; Resuscitation; Rwanda; San Francisco; Savings; Scientist; Series; Severities; Severity of illness; Solid; Training; Ultrasonography; Universities; World Health Organization; base; care delivery; career; cooking; cost; cost effective; cost effectiveness; design; evidence base; experience; global health; hemodynamics; improved; international center; low and middle-income countries; low income country; medical schools; mortality; novel diagnostics; parkin gene/protein; prevent; public health relevance; research study; skills; standard of care; tool; trial comparing

DESCRIPTION (provided by applicant): Diarrhea causes nearly two million deaths annually in children under five, or one fifth of all child deaths worldwide. As the severity of the disease depends on the degree of fluid loss, accurately assessing dehydration status remains a crucial step in preventing morbidity and mortality. While children with severe dehydration require immediate treatment with intravenous fluids to prevent hemodynamic compromise and death, children with mild to moderate dehydration have a significant reduction in hospital length of stay and fewer adverse events when treated with relatively inexpensive oral rehydration solution (ORS) as compared to treatment with costly intravenous fluids. While the World Health Organization (WHO) recommends using a four-point clinical scale for determining the severity of dehydration in children, this scale has never been validated against a physiologic gold standard (such as the accepted standard of percent weight change with rehydration). While several prior authors have developed alternative clinical prediction rules for severe dehydration in children, these scales have not been externally validated against a physiologic gold standard in a developing country, where the vast majority of pediatric deaths from diarrhea occur, and where clinician expertise and varying disease patterns may affect the accuracy of any clinical scale derived in a developed country. There is an urgent need for research into new clinical tools that can accurately and reliably assess dehydration in a resource-limited setting. As part of this K01 award, we will conduct a series of three studies that will derive, validate, and assess the reliability of a new clinical prediction rule for severe dehydration in children with diarrhea in te developing world. In addition, we will validate and assess the reliability of ultrasound of the inferior vena cava (IVC) for predicting severe dehydration in children with diarrhea in the developing world. Finally, we will compare the accuracy of each of these new diagnostic tools to that of the WHO scale, using percent weight change with rehydration as the gold standard for all of our measures of dehydration, in order to determine whether either of these new methods may improve upon the current standard of care. My prior training and research experience have provided me with a solid foundation for this career development award. I have completed a Doctorate of Medicine at the University of California, San Francisco and a Masters of Public Health in International Health at the University of California, Berkeley. I also have experience designing and managing two small research studies conducted in resource-limited settings, including one study providing preliminary data for this International Research Scientist Development Award (IRSDA) application. However, I would benefit from additional targeted training in specific areas, including advanced regression analysis and recursive partitioning, clinical trial design and management, cost- effectiveness analysis, the pathophysiology of diarrhea and malnutrition, and the ethics of conducting research in resource-limited settings, which will be completed during the five years of this K01 award through formal coursework, seminars, directed reading, and individualized tutorials. I will also benefit from the additional experience of managing large, prospective studies under the mentorship of three scientists with extensive experience in conducting public health and global health research, including Dr. Jennifer Friedman of Brown Medical School, Dr. Nur Haque Alam of the International Center for Diarrheal Disease and Research, Bangladesh (ICDDRB), and Dr. Earl F. Cook of the Harvard School of Public Health. After this K01 award, I plan to apply for an R01 grant to fund a randomized controlled trial comparing these new methods for diagnosing and managing dehydration in children with diarrhea to the current standard of care, analyzing both health-related outcomes, such as adverse events, and total costs. Improved methods for assessing severe dehydration have the potential to help clinicians in the developing world identify the children with diarrhea at greatest need for emergent intervention, while also preventing the adverse events and wasted resources associated with the inappropriate use of intravenous fluids. These new methods have the potential to improve the delivery of care in both developed and developing country hospitals and clinics, as well as in refugee camp settings where outbreaks of diarrheal disease are common. In addition to funding research into the development of these new methods, the IRSDA will also provide me with the support necessary to launch my career as an independently funded physician-scientist in translational global health research. Utilizing the knowledge and skills gained as part of the IRSDA, I am committed to a career aimed at improving the evidence base for the diagnosis and management of dehydration in resource-limited settings, thereby improving both the effectiveness and cost- effectiveness of care and potentially saving thousands of lives each year.

描述（由申请人提供）：腹泻每年导致近 200 万名五岁以下儿童死亡，占全世界儿童死亡人数的五分之一。由于疾病的严重程度取决于体液流失的程度，准确评估脱水状态仍然是预防发病和死亡的关键步骤。虽然严重脱水的儿童需要立即静脉输液治疗，以防止血流动力学受损和死亡，但与轻度至中度脱水的儿童相比，使用相对便宜的口服补液盐 (ORS) 治疗时，住院时间显着缩短，不良事件也更少。接受昂贵的静脉输液治疗。虽然世界卫生组织 (WHO) 建议使用四点临床量表来确定儿童脱水的严重程度，但该量表从未根据生理金标准（例如补液时体重变化百分比的公认标准）进行验证。虽然几位先前的作者已经制定了儿童严重脱水的替代临床预测规则，但这些量表尚未根据发展中国家的生理黄金标准进行外部验证，因为绝大多数儿科死亡都发生在发展中国家，而且临床医生的专业知识和不同的水平疾病模式可能会影响发达国家得出的任何临床量表的准确性。迫切需要研究新的临床工具，以便在资源有限的情况下准确可靠地评估脱水情况。作为 K01 奖项的一部分，我们将开展一系列三项研究，这些研究将推导、验证和评估发展中国家腹泻儿童严重脱水的新临床预测规则的可靠性。此外，我们将验证和评估下腔静脉 (IVC) 超声预测发展中国家腹泻儿童严重脱水的可靠性。最后，我们将使用补液后的体重变化百分比作为我们所有脱水测量的黄金标准，将每种新诊断工具的准确性与世界卫生组织量表的准确性进行比较，以确定这些新方法中的任何一种是否可以改善当前的护理标准。我之前的培训和研究经历为我获得这一职业发展奖奠定了坚实的基础。我在加州大学旧金山分校获得了医学博士学位，在加州大学伯克利分校获得了国际卫生公共卫生硕士学位。我还拥有设计和管理在资源有限的环境中进行的两项小型研究的经验，其中一项研究为国际研究科学家发展奖 (IRSDA) 申请提供了初步数据。然而，我将从特定领域的额外有针对性的培训中受益，包括高级回归分析和递归划分、临床试验设计和管理、成本效益分析、腹泻和营养不良的病理生理学以及在资源有限的环境中进行研究的伦理学，将在 K01 奖项的五年内通过正式课程、研讨会、定向阅读和个性化教程完成。我还将受益于在三位科学家的指导下管理大型前瞻性研究的额外经验，这些科学家在公共卫生和全球健康研究方面拥有丰富的经验，其中包括布朗医学院的詹妮弗·弗里德曼博士、国际癌症研究所的努尔·哈克·阿拉姆博士。孟加拉国腹泻病与研究中心 (ICDDRB) 和哈佛大学公共卫生学院的 Earl F. Cook 博士。在获得 K01 奖项后，我计划申请 R01 拨款来资助一项随机对照试验，将这些诊断和管理腹泻儿童脱水的新方法与当前的护理标准进行比较，分析与健康相关的结果，例如不良事件和总成本。评估严重脱水的改进方法有可能帮助发展中国家的临床医生识别最需要紧急干预的腹泻儿童，同时还可以防止因静脉输液不当使用而导致的不良事件和资源浪费。这些新方法有可能改善发达国家和发展中国家的医院和诊所以及腹泻病常见爆发的难民营环境中的护理服务。除了资助这些新方法的开发研究外，IRSDA 还将为我提供必要的支持，以启动我作为一名独立资助的医师科学家从事转化性全球健康研究的职业生涯。利用作为 IRSDA 的一部分获得的知识和技能，我致力于改善资源有限环境中脱水诊断和管理的证据基础，从而提高护理的有效性和成本效益，并潜在地提高脱水的有效性和成本效益。每年拯救数千人的生命。

项目成果

Accuracy of Inferior Vena Cava Ultrasound for Predicting Dehydration in Children with Acute Diarrhea in Resource-Limited Settings.

下腔静脉超声预测资源有限环境中急性腹泻儿童脱水的准确性。

• 发表时间: 2016
• 影响因子: 3.7
• 作者: Modi, Payal;Glavis;Nasrin, Sabiha;Guy, Allysia;Chowa, Erika P;Dvor, Nathan;Dworkis, Daniel A;Oh, Michael;Silvestri, David M;Strasberg, Stephen;Rege, Soham;Noble, Vicki E;Alam, Nur H;Levine, Adam C
• 通讯作者: Levine, Adam C

Empirically Derived Dehydration Scoring and Decision Tree Models for Children With Diarrhea: Assessment and Internal Validation in a Prospective Cohort Study in Dhaka, Bangladesh.

腹泻儿童的脱水评分和决策树模型：孟加拉国达卡前瞻性队列研究的评估和内部验证。

• 发表时间: 2015-08-18
• 作者: Levine, Adam C;Glavis;Modi, Payal;Nasrin, Sabiha;Rege, Soham;Chu, Chieh;Schmid, Christopher H;Alam, Nur H
• 通讯作者: Alam, Nur H

Midupper Arm Circumference Outperforms Weight-Based Measures of Nutritional Status in Children with Diarrhea.

中上臂围优于基于体重的腹泻儿童营养状况测量。

• 发表时间: 2015-07
• 作者: Modi, Payal;Nasrin, Sabiha;Hawes, Meagan;Glavis;Alam, Nur H;Hossain, M Iqbal;Levine, Adam C
• 通讯作者: Levine, Adam C

Sex and Gender Differences in Acute Pediatric Diarrhea: A Secondary Analysis of the DHAKA Study.

急性小儿腹泻的性别差异：达卡研究的二次分析。

• 发表时间: 2018
• 作者: Jarman, Angela F;Long, Sara E;Robertson, Sarah E;Nasrin, Sabiha;Alam, Nur Haque;McGregor, Alyson J;Levine, Adam C
• 通讯作者: Levine, Adam C

Prediction of severe disease in children with diarrhea in a resource-limited setting.

在资源有限的环境中预测腹泻儿童的严重疾病。

• 发表时间: 2013
• 影响因子: 3.7
• 作者: Levine, Adam C;Munyaneza, Richard M;Glavis;Redditt, Vanessa;Cockrell, Hannah C;Kalimba, Bantu;Kabemba, Valentin;Musavuli, Juvenal;Gakwerere, Mathias;Umurungi, Jean Paul de Charles;Shah, Sachita P;Drobac, Peter C
• 通讯作者: Drobac, Peter C